In an interview with Pharmacy Times®, Joshua K. Sabari, MD, assistant professor at the Department of Medicine at NYU Grossman School of Medicine, discussed zongertinib’s (Hernexeos; Boehringer Ingelheim) most common adverse events and its positive impact on patients’ daily lives. Sabari noted that pharmacists should monitor for diarrhea and mild liver enzyme elevations, especially during the first 12 weeks of treatment. Unlike intravenous therapies, zongertinib provides stable symptom relief and functional status, offering patients a convenient oral option with fewer chemotherapy-like toxicities and a significantly improved quality of life.
This is part 2 of a 3-part video series. You can watch part one here.
This transcript was edited for grammar and clarity using artificial intelligence.
Pharmacy Times: What key adverse events should pharmacists and clinicians be prepared to manage with zongertinib tablets, and what counseling points are crucial for patients starting this treatment?
Key Takeaways
- Pharmacists should monitor diarrhea and liver enzymes closely during early zongertinib therapy.
- Oral therapy allows patients to maintain stable symptom control without frequent clinic visits.
- Zongertinib improves patient-reported outcomes compared to chemotherapy or IV antibody-drug conjugates.
Joshua K. Sabari, MD: Zongertinib is a HER2-specific tyrosine kinase inhibitor, and it spares EGFR, so we don’t see the cutaneous toxicities common with other HER2 and EGFR inhibitors. The most common adverse event is diarrhea. Grade 1 and grade 2 diarrhea occur in about 50% of patients, but grade 3, clinically significant diarrhea is low at about 1%. We also see mild elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in fewer than 10% of patients, so it’s important to monitor liver function tests every 2 weeks for the first 12 weeks of therapy. We don’t see cardiac dysfunction or significant interstitial lung disease. Overall, zongertinib is one of the better-tolerated targeted therapies available.
Pharmacy Times: For patients with HER2-mutant NSCLC, what does having an oral treatment option like zongertinib tablets mean for their daily lives, and what are the key advantages of this method over an intravenous therapy?
Sabari: When we meet a patient with stage 4 cancer, we explain that it’s treatable, but not curable. The goals of systemic therapy are to improve quality of life and hopefully extend survival. There are 3 types of systemic therapies: chemotherapy, immunotherapy, and true targeted therapy. An antibody-drug conjugate is essentially targeted chemotherapy—it has a warhead attached to an antibody, but the payload still causes chemotherapy-like toxicities. It also requires IV infusion once every 3 weeks, and patients often experience fatigue and nausea for several days after treatment.
With an oral therapy like zongertinib, how a patient feels on day 1 is how they’ll feel on day 3 or day 15. At ASCO 2025, we presented patient-reported outcomes showing dramatic improvements in symptoms like cough and shortness of breath, as well as overall functional status. These improvements remain stable over time. In contrast, patients treated with chemotherapy or antibody-drug conjugates often experience a steady decline in functional status due to side effects.